Motor Axonal Regeneration after Partial and Complete Spinal Cord Transection

The Journal of Neuroscience, 2012 · DOI: 10.1523/JNEUROSCI.0308-12.2012 · Published: June 13, 2012

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Researchers investigated methods to encourage nerve fiber regrowth after spinal cord injuries in rats. The goal was to see if combining treatments could help motor axons (nerve fibers that control movement) regenerate across the damaged area of the spinal cord. The treatments included injections to stimulate nerve growth, supportive cell transplants to create a permissive environment, and growth factors to guide the regenerating axons. They tested these approaches in both partial and complete spinal cord injury models. While the combined treatments did promote some nerve fiber regrowth and synapse formation, the functional outcomes were not always positive. In some cases, the treatments worsened motor function or increased spasticity, highlighting the complexity of spinal cord repair.

Study Duration

3 Months

Participants

85 adult female Fischer 344 rats

Evidence Level

Level II; Experimental Study

Key Findings

1
Combinatorial treatment with cAMP injections, bone marrow stromal cell grafts, and BDNF gradients resulted in motor axon regeneration beyond both C5 hemisection and T3 complete transection sites in rats.
2
Despite motor axon regeneration and synapse formation, motor outcomes worsened after partial cervical lesions and spasticity worsened after complete transection.
3
Regenerating axons exhibited chemotropic attraction and guidance to the growth factor BDNF, and the regeneration of host axons was entirely restricted to regions of BDNF expression.

Research Summary

This study investigated the efficacy of combinatorial treatments in promoting motor axonal regeneration after partial and complete spinal cord transections in rats. The treatments included cAMP injections, bone marrow stromal cell grafts, and gradients of BDNF. The results demonstrated that combinatorial treatment led to motor axon regeneration beyond both C5 hemisection and T3 complete transection sites. However, despite synapse formation, functional outcomes were not improved, and in some cases, worsened. The study highlights the complexity of spinal cord repair and the need for additional control and shaping of axonal regeneration to achieve meaningful functional recovery.

Practical Implications

Refine Treatment Strategies

Future therapies need to focus on controlling the direction and specificity of axonal regeneration to ensure appropriate connections are formed.

Temporal Control of Growth Factors

Investigate transient growth factor expression to promote initial axonal growth without causing long-term side effects like spasticity.

Integrate Rehabilitation Strategies

Combine axonal regeneration therapies with targeted rehabilitation programs to enhance functional outcomes.

Study Limitations

1
Functional outcomes were potentially masked by the activation of spinal reflex activity and spasticity.
2
The study highlights the complexity of efforts to reconstruct injured adult neural circuitry.
3
Adverse functional outcomes may have resulted from formation of contacts by regenerating axons with inappropriate target neurons.

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